This invention relates to dermatology and cell biology.
Skin includes a surface layer, known as the epidermis, and a deeper connective tissue layer, known as the dermis. The epidermis undergoes continuous turnover as the outermost cells are exfoliated and replaced by cells that arise from inner dermal layers. The dermis is composed of a variety of cell types, including fibroblasts.
Skin thickness begins to decline in humans after the age of 20 as the dermis becomes thinner and the number of skin fibroblasts declines. As skin ages, or is exposed to UV light and other environmental insults, changes in the underlying dermis can lead to the functional and morphological changes associated with damaged skin. Decreases in the abundance and function of products of the fibroblasts, which include collagen and proteoglycans, are believed to play major roles in wrinkled and damaged skin.
We have discovered that adenosine stimulates DNA synthesis, increases protein synthesis, and increases cell size in cultures of human skin fibroblasts. Based on this discovery, the invention provides methods and compositions for enhancing the condition of skin.
In general, the invention provides a method for enhancing the condition of non-diseased skin of a mammal, e.g., a human. The method includes topically applying a therapeutically effective amount of a composition including adenosine or an adenosine analog to non-diseased skin of the mammal.
The invention also provides a method for promoting healing of broken, non-diseased skin in a mammal by topically administering a composition including a therapeutically effective amount of adenosine or an adenosine analog to the mammal.
Also included in the invention is a method for increasing DNA synthesis in a dermal cell of non-diseased skin of a mammal. The method includes topically administering a therapeutically effective amount of adenosine or an adenosine analog to a region of non-diseased skin of the mammal containing dermal cell. The adenosine is added so that it does not cause proliferation of the dermal cell.
The invention also features a method of increasing protein synthesis in a dermal cell of non-diseased skin of a mammal. The method includes topically administering a composition including a therapeutically effective amount of adenosine or an adenosine analog to a region of skin of the mammal containing the dermal cell. The adenosine or adenosine analog does not cause proliferation of the dermal cell.
Also provided in the invention is a method of increasing cell size in a dermal cell in non-diseased skin of a mammal, e.g., a human. The method includes topically administering a composition including a therapeutically effective amount of adenosine to a region of skin of the mammal containing the dermal cell, wherein addition of the adenosine does not cause proliferation of the dermal cell, wherein addition of the adenosine does not cause proliferation of the dermal cell.
The invention also includes a method for enhancing skin condition in a mammal, e.g., a human. The method includes providing fibroblasts from the mammal ex vivo, culturing the fibroblasts in the presence of adenosine, and reintroducing the fibroblasts into the mammal.
The therapeutically effective amount of adenosine used in the above-described methods is preferably 10xe2x88x923 M to 10xe2x88x927 M, more preferably 10xe2x88x924 M to 10xe2x88x926 M, and most preferably about 10xe2x88x924 M.
The composition used in the above-described methods can include a second agent in addition to adenosine. The second agent can be, e.g. an agent that promotes binding of adenosine or an adenosine analog to an adenosine receptor, an angiogenic factor such as vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (BFGF), an agent that itself enhances skin condition, such as tretoinin or another known conditioning agent such as an emollient, a humectant, or an occlusive agent.
In preferred embodiments of the invention, the adenosine or an adenosine analog does not promote skin cell proliferation.
The invention also provides a composition including about 10xe2x88x923 M to about 10xe2x88x927 M adenosine and a therapeutically effective amount of an angiogenesis factor. In some embodiments, the composition of the adenosine is about 10xe2x88x924 M.
As used herein, xe2x80x9cenhancement of skin conditionxe2x80x9d means a noticeable decrease in the amount of wrinkling, roughness, dryness, laxity, sallowness, or pigmentary mottling in skin.
As used herein, a xe2x80x9ctherapeutically effective amountxe2x80x9d of adenosine or an adenosine analog means an amount that enhances skin condition when applied to skin.
As used herein, xe2x80x9cnon-diseased skinxe2x80x9d means skin free of any proliferative disorder observable by visual inspection.
The present invention advantageously allows for enhancement of skin condition. This results in skin that shows a less wrinkled, rough, or dry complexion. For example, the invention provides for enhancing the condition of skin damaged due to exposure to the sun or skin whose condition has deteriorated due to normal aging.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of this invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.